Cancer is a collection of myriad diseases, each of which has a unique molecular signature and drug response profile. For example, colorectal cancer may be any one of hereditary nonpolyposis colorectal cancer, familial adenomatous polyposis, and Gardner syndrome. Furthermore, any particular cancer may be associated with distinct molecular lesions, such as wnt signaling dysregulation, p53 and other DNA repair and apoptosis dysregulation, growth factor signaling and other oncogene dysregulation, or any combination thereof. Thus, cancer, such as prostate cancer, breast cancer, colorectal cancer, lung cancer, or pancreatic cancer, may be further subdivided into specific molecular diseases, each of which has its own diagnostic or prognostic indicators and therapeutic responses.
There is a continuing medical need for specific tests to diagnose the particular nature of a cancer, and to determine whether a patient is likely to respond to a particular therapy. VEGF antagonists are a class of therapeutics intended to treat cancer by abrogating or otherwise altering the vascularization of tumors. The effectiveness of these drugs depends in part on the specific type of cancer and other factors associated with the physiology of the patient. The development of a prognostic biomarker assay or patient stratification protocol will enable the physician to select those patients who are most likely to respond favorably to therapy, and to monitor a patient's response to a therapy.
Several biomarkers can predict how a patient will respond to VEGF antagonist (e.g., aflibercept and bevacizumab) therapy. Those biomarkers include E-selectin, bFGF, ICAM, and VEGF (Calleri et al., Clin Cancer Res 2009, 15(24):7652-7657; Dowlati et al., Clin Cancer Res 2008, 14(5):1407-1412.) VEGF is found in several isoforms: VEGF-A206, VEGF-A189, VEGF-A165, VEGF-A145, VEGF-A121, VEGF-B, VEGF-C and VEGF-D. VEGF-A206, VEGF-A189 and VEGF-A165, bind to neuropilin-1 (“NRP1”) as well as VEGF receptors 1 and 2 (reviewed in Neufeld et al., FASEB J., 1999, 13:9-22).